This research study will test OT-82, which is an investigational ("research" or
"experimental" ) drug. The study has two stages (Stage 1 and Stage 2). The purpose of Stage 1
is to determine the safety and tolerability and the maximum tolerated dose (MTD) or the
maximum tested dose of OT-82 administered orally to participants. The purpose of Stage 2 is
to determine the preliminary efficacy of OT-82 in relapsed or refractory lymphoma at the MTD
or the maximum tested dose. Both parts of the study will also evaluate the pharmacokinetics
(absorption, distribution, metabolism, elimination) of OT-82.
OT-82 treatment slowed the growth, reduced the size, or in some cases cured certain cancers
in animal studies. It is hoped that participants with relapsed or refractory lymphoma treated
with OT - 82 in this study will experience slowing tumor growth and/or reduction of tumor
- Age ≥ 18 years.
- Provides signed informed consent before initiation of any study-specific procedures or
- Histologically (tumor tissue) confirmed diagnosis of lymphoma that has progressed
despite prior treatment, and for which additional options leading to meaningful
clinical benefit are not available. Lymphoma diagnoses may include the following:
a. Confirmed histological diagnosis of the following types of B-cell Non-Hodgkin
lymphoma (NHL): i. Low-grade B-cell NHLs including, but not limited to, FL, MCL, MZL,
PMBL, LPC, or CLL/SLL. ii. Intermediate to high grade B-cell NHLs including, but not
limited to DLBCL and other intermediate grade B-cell NHL, with disease progression
following stem cell transplant or patient must be unwilling, unable or not an
appropriate candidate for such. iii. Transformed Follicular Lymphoma. b. PTCL and
others T-cell lymphoma, in which there is measurable non-cutaneous disease.
c. Hodgkin's Lymphoma
- Measurable disease in all lymphoma classes except PTCL.
1. Defined as nodal lesions >1.5 cm or extra-nodal, non-cutaneous lesions > 1.0 cm.
2. Target lesions that have been previously irradiated and have not progressed since
radiation are not considered measurable.
3. Patients with PTCL may be eligible if they do not have measurable disease if they
have skin disease.
- ECOG performance status of 0 or 1. This is a measure of a participant's ability to
manage self care, mobility, work status, and other measures.
- Adequate baseline organ function.
- Adequate baseline hematologic (blood) function.
- Negative blood pregnancy test result obtained during screening if the patient is
sexually mature woman who has not undergone a hysterectomy or ovary removal or has not
been naturally postmenopausal for at least 24 consecutive months.
- Participant agrees to use acceptable contraceptive methods for the duration of time on
the study, and continue to use acceptable contraceptive methods for 3 months after the
last treatment with OT-82:
- Participant agrees to, and be capable of, adhering to the study visit schedule and
other protocol requirements, including follow-up for survival.
- Persistent clinically significant toxicities from previous anticancer therapy
(excluding alopecia, which is permitted, and excluding Grades 2 and 3 laboratory
abnormalities if they are not associated with symptoms, are not considered clinically
significant by the Investigator, and can be managed with available medical therapies).
- Treatment with cytotoxic, biologic, or targeted therapies for lymphoma within 14 days
before administration of the patient's first dose of OT-82.
- Treatment with an investigational drug within 28 days before administration of the
patient's first dose of OT-82.
- Treatment with a stem cell transplant with an infusion of stem cells no less than 8
weeks before administration of the patient's first dose of OT-82. There should be no
graft versus host disease > Grade 1 and participant should have discontinued all
immunosuppressive therapy for such ≥ 2 weeks from OT-82 treatment.
- Radiation therapy within 14 days before administration of the patient's first dose of
- Major surgical procedure within 28 days before administration of the patient's first
dose of OT-82.
- Physical abnormality or medical condition that limits swallowing oral solutions,
and/or has a history of non-adherence to oral therapies.
- Clinically significant gastrointestinal disorder that may alter absorption such as
malabsorption syndrome or major resection of the stomach or bowels
- Additional active malignancy that may confound the assessment of the study endpoints.
If the participant has a past cancer history (i.e. active malignancy within 2 years
before study entry) with substantial potential for recurrence, this must be discussed
with the Sponsor before study enrollment. Patients with the following concomitant
neoplastic diagnoses are eligible: nonmelanoma skin cancer and carcinoma in situ
(including transitional cell carcinoma, cervical cancer, anal carcinoma, and melanoma
- Clinically significant cardiovascular disease including, but not limited to:
1. Uncontrolled or any New York Heart Association Class III or IV congestive heart
2. Uncontrolled angina, history of myocardial infarction, unstable angina, or stroke
within 6 months before study entry.
- Systolic blood pressure > 170 mm Hg or diastolic blood pressure > 110 mm Hg, or
clinically significant arrhythmias not controlled by medication.
- Average QTc interval by QTcF on triplicate ECGs at screening or baseline > 470 msec
(females) or > 450 msec (male).
- History of additional risk factors for a cardiac condition known as torsade de pointes
(e.g., heart failure, low potassium, family history of long QT syndrome, use of
concomitant medications that prolong the cardiac QT/QTc interval).
- Uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive
pulmonary disease, pulmonary hypertension) that, in the opinion of the Investigator,
would put the patient at significant risk for pulmonary complications during the study
(patient must not be dependent on oxygen).
- History of brain or leptomeningeal malignant disease (CNS imaging is not required
before study entry unless there is a clinical suspicion of CNS involvement).
- Primary CNS lymphoma.
- Condition requiring systemic treatment with either corticosteroids (> 10 mg daily
prednisone equivalents) or other immunosuppressive medications within 14 days before
administration of the patient's first dose of OT-82. Inhaled or topical steroids and
adrenal replacement doses ≤ 10 mg daily prednisone equivalents are permitted in the
absence of active autoimmune disease.
- Uncontrolled illness including, but not limited to, uncontrolled infection,
disseminated intravascular coagulation, or psychiatric illness/social situations that
would limit compliance with study requirements.
- Known positive status for HIV and:
1. Not receiving optimal anti-HIV therapy
2. Demonstrated to be noncompliant with anti-HIV therapy.
3. Has evidence of worsening HIV viral load (as assessed by HIV real-time qPCR).
4. Not willing to attend HIV clinic follow-up at appropriate intervals.
- Active or chronic hepatitis B or hepatitis C (screening is not required).
- Any medical condition that, in the opinion of the Investigator, places the patient at
unacceptably high risk for toxicity.
- Anticoagulation with warfarin or a direct thrombin inhibitor; a washout period of 7
days before administration of a patient's first dose of study drug is required for
patients who are taken off these treatments (treatment with low molecular weight
heparin is allowed).
- Requires a medication(s) that is a strong inhibitor of cytochrome CYP3A4
(boceprevir,clarithromycin, cobicistat, conivaptan, diltiazem, anoprevir/ritonavir,
elvitegravir/ritonavir, grapefruit juice, idelasib, indinavir/ritonavir, itraconazole,
ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir,
paritaprevir/ritonavir/ombitasvir and/or dasabuvir, posaconazole, ritonavir,
saquinavir/ritonavir, tipranavir/ritonavir, troleandomycin, voriconazole, and
- Requires a medication(s) that is a strong inducer of CYP3A4 (carbamazepine,
enzalutamide, mitotane, phenytoin, rifampin, and St John's wort).
- Requires a medication(s) that is a strong inhibitor of P-glycoprotein (P-gp)
(amiodarone, carvedilol, clarithromycin, cyclosporine, dronedarone, elacridar,
itraconazole, ketoconazole, lapatinib, lopinavir/ritonavir, propafenone, quinidine,
ranolazine, reserpine, ritonavir, saquinavir/ritonavir, tacrolimus, telaprevir,